Fluorescence imaging technology is a very powerful tool for disease detection, diagnosis and even surgical guidance, resulting from its the advantages of high sensitivity, ease of operation and non-destructive real-time tracking. Well-designed contrast agents such as organic dyes are critical to obtain high-quality fluorescence imaging. Due to strong intermolecular interactions, tradtional organic fluorescent materials encounter aggregation-caused quenching (ACQ) problem and emit weakly in aggregates, leading to their low signal and poor sensitivity in fluorescence imaging. In contrast to ACQ materials, aggregation-induced emission fluorogens (AIEgens) show weak emission in solution but bright emission in aggregates or solid, enabling their great potential in biomedical therapeutic applications. The development of high-performance theranostic platforms is always an intractable challenge in modern medicine research. And it is highly desirable to develop luminescent materials with highly efficient anticancer efficacy. Thus, in this thesis, we developed a series of novel AIEgens and discussed their potential clinical applications in bioimaging and therapy for cancer.

Firstly, we introduced triphenylamine and indanedione as the donor (D) unit and acceptor (A) unit, respectively, to design a novel dual-functional D-A photosensitizer 4,4'-(((4-((1,3-dioxo-1H-inden-2(3H)-ylidene)methyl)phenyl)azanediyl)bis(4,1-phenylene))bis(1-methylpyridin-1-ium) iodide (ITPM) with AIE characteristics that not only can perform ultra-efficient photodynamic therapy (PDT) towards drug-resistance tumor, but also can simultaneously self-report its real-time treatment progress by fluorescence imaging. It was well demonstrated that AIE-active ITPM undergoes a cell membrane-to-nucleus translocation with time during PDT progress, thus enabling the real-time and in-situ monitoring via fluorescence migration. This specialty is also tactfully utilized to report the therapeutic effect of different clinical chemotherapeutic drugs. Such real-time monitoring when performing cancer therapy is vitally important for lessening non-specific damage and achieving precise therapy. More impressively, AIE-active ITPM can act as an ultra-efficient photosensitizer to exert high-efficiency therapy towards different drug-resistance tumors, expected to tackle the issue of clinical drug resistance.

New luminescent materials that possess the advantages of high sensitivity, high resolution, and deep tumor-penetrating imaging as well as bimodal synergistic therapeutic functions may be one of the best potential alternatives for efficient theranostics. Therefore, by incorporating a AIE-active and near-infrared (NIR)-emissive core (3-(5-(4-(phenyl(4'-(1,2,2-triphenylvinyl)-[1,1'-biphenyl] -4-yl)amino)phenyl)thiophen-2-yl)-2-(pyridin-4-yl)acrylonitrile, TPE-TTPy) and a Au(I) moiety, we further developed a powerful Au(I)-containing AIEgen (TPE-TTPy-Au) with integrated multifunctions of bimodal imaging and bimodal combination therapy. This simple small-molecule system could simultaneously realize high-contrast fluorescence imaging and computed tomography imaging. Additionally, TPE-TTPy-Au could act as an effective thioredoxin reductase inhibitor to exert inherent anticancer effect, and simultaneously could work as an ideal radiosensitizer to produce efficient anticancer efficacy through a bimodal synergistic effect.

Overall, our exploration on the development of novel AIEgens with high-performance theranostics can give a new design guideline to obtain AIE luminogens with extraordinary functions and can open a new avenue to develop new luminescent theranostic systems.